This invention relates to granulated psyllium compositions which are readily dispersible in water and aqueous beverages.
Powdered husks of the psyllium seed is a common and effective bulk laxative drug. The hydrophilic properties of this natural fibrous laxative causes ingested does to absorb large amounts of water, thus producing bulk and normalizing regularity through proper stool formation.
The single normal adult dose is about 3 grams of psyllium powder which is dispersed by the user in water or an aqueous beverage. Powdered psyllium has very poor wetting capabilities and therefore must be vigorously mixed with aqueous fluids to produce a palatable dispersion.
Historically, psyllium seed preparations have been formulated to contain equal parts of active bulk laxative and a sugar (usually dextrose) as a means of promoting dispersion ease. These 50:50 dilutions are also inconvenient to the user since mixability is still often difficult. Rigorous agitation and/or stirring are required to render the composition palatable and lump free. Moreover, patients on restricted sugar-free or weight controlling diets cannot normally use these products.
Attempts to improve mixability have led to effervescent powder formulas which at best still contain only about 50% of active bulk laxative, are usually high in sugar content and contain significant amounts of sodium or potassium ion, which preclude their use by diabetic patients and patients on low sodium diets.
Pure psyllium powder resists wetting in water or aqueous beverages because of its fine particle size and the inability of water to penetrate the powder mass due to fast surface hydration and swelling. Vigorous agitation in water results in a lumpy dispersion. The lumps, although wetted on their outer surface, contain dry undispersed powder on the inside. Fluid penetration must precede hydration in order to accomplish instant wettability and dispersability.
The wettability of powdered psyllium can be enhanced by diluting the particles with large amounts of a highly water soluble material, e.g., sucrose. The disadvantages of doing so have been discussed above. Moreover, lumping is not totally avoided because in order to do so, the water soluble material must impart dilation to the psyllium powder, viz., the creation of voids between the individual particles which hold them apart long enough to allow the individual particles to become wet rather than agglomerated into clumps. As stated above, sugars have been used for this purpose with limited success. Effervescent sugar-psyllium mixtures self-dilate when carbon dioxide is released upon use. It follows therefore, that air alone should act as a diluent for a bed of pysllium if the bed were properly mechanically dilated.
However, neither dilation alone nor the water solubility of the coating agent ensures rapid and complete dispersibility of powdered psyllium in water and aqueous beverages. Although a number of water soluble or dispersible polymers can be used to achieve dilation of powdered psyllium by conversion thereof into granules in which the psyllium particles are diluted with air voids, instant and complete dispersibility of the resulting product in water and aqueous beverages is rarely achieved employing amounts thereof which could form alcoholic solutions of a viscosity low enough to be used to granulate the psyllium.
A wetting test was developed to show the effect of various polymers on the wettability of psyllium granules produced by wet granulation of psyllium powder with solutions thereof. The time required to completely wet 3.7 g of psyllium ladled onto the surface of 150 ml. of water (or aqueous beverage) in a 65 ml diameter beaker was measured. If greater than 2 minutes was required for wetting, the wetting time was recorded as greater than 120 seconds.
Table I below lists the results of attempts to accomplish more rapid wetting of psyllium with glycerin, which theoretically should enhance dispersibility of the psyllium by increasing the surface wetting of the psyllium powder. Alcoholic (anhydrous ethanol) solutions of glycerin with or without Tween 80, a surface active agent, were added to psyllium powder. Thorough mixing of the wetted powder insured total distribution of the ingredients. The alcohol was evaporated, the powders were sized and treated. It was found that even when a strong wetting agent was added, glycerin did not enhance wettability. Only with equal parts of psyllium and dextrose did a mixture of glycerin and wetting agent produce fast wetting because although glycerin should have been a good wetting bridge between psyllium and water, it did not impart any dilation to the powder mass. In fact, the quick hydration at the powder-water interface actually impeded penetration of the water and complete wetting of all the particles was prevented. By dilution with 50% dextrose, dilation of the psyllium in effect was accomplished and penetration of the water preceded hydration and, with the aid of the glycerin and wetting agent, fast lump-free wetting occurred. However, the resulting product had the other disadvantages discussed above.
TABLE I ______________________________________ Wetting Contents % Time Psyllium Dextrose Glycerin Tween 80 (sec.) ______________________________________ 50 50 -- -- &gt;120 50 48.4 1.5 0.1 10 75 23.4 1.5 0.1 &gt;120 98.4 0 1.5 0.1 &gt;120 96.9 -- 3.0 0.1 &gt;120 97.9 -- 2.0 0.1 &gt;120 97.0 -- 3.0 -- &gt;120 95.0 -- 5.0 -- &gt;120 ______________________________________
Table II below gives the wetting times obtained with various polymeric and other materials used to achieve mechanical dilation by wet granulation of the psyllium powder from an alcoholic (95% denatured) solution of the selected material. Agglomeration of psyllium particles effectively achieved mechanical dilation by dilution with air voids. The concentrations thereof employed were dictated by the viscosity of the solutions thereof or toxicity considerations. Although dilation was accomplished in all cases except one (Pluronic a S.A.A.), fast aqueous penetration and uniform wetting was only occasionally achieved.
TABLE II ______________________________________ Psyllium Content Polymer ______________________________________ 100% None &gt;120 98% Methocel E-15 2% &gt;120 99.8% Carbopol 0.2% &gt;120 99% Methocel E-15 1% 90 99% Pluronic F-68 1% &gt;120 99% Gantrez-AN119 1% &gt;120 98% Xanthan Gum 2% &gt;120 95% Sucrose Syrup 5% &gt;120 99% PVP 1% 22 99% PEG 1% (3350) 30 ______________________________________
Notwithstanding the foregoing results, we have found that certain of the foregoing polymers can be employed in a wet granulation process at higher concentrations to produce granulated psyllium products which not only have a high psyllium content (greater than 90% and usually at least about 95%) but which are substantially instantly and uniformly dispersible in water and aqueous beverages.
Polyvinylpyrrolidone (PVP) is one of the polymers which proved to be operable at concentrations above about 2%. U.S. Pat. No. 2,820,741 teaches the use of an alcoholic solution of PVP as a granulating agent for water-insoluble materials which are unstable in the presence of water and that PVP aids in the physical disintegration of granules when formed into tablets or filled into capsules. However, it teaches nothing about the effect thereof upon the dispersibility of such granulated materials in water. U.S. Pat. No. 3,725,541 discloses the use of a water insoluble polymer or copolymer of vinylpyrrolidone and powdered sugar to produce a granulated anti-diarrhea product. Other patents which disclose a process of preparing a pharmaceutical by the addition of the active ingredient to an alcoholic PVP solution are U.S. Pat. Nos. 3,089,818; 3,257,277; 3,553,313; 3,673,163; and 4,081,529. We have also found that polyethylene glycol (PEG) is superior to PVP in achieving rapid dispersibility of the psyllium in water at concentrations above about 1.5% by weight of the psyllium. Patents which employ PEG in the preparation of pharmaceutical products are U.S. Pat. Nos. 2,698,822; 2,540,253; 3,308,217; 3,862,311; 3,932,613; and 4,151,273. Gakenheimer (U.S. Pat. No. 2,540,253) discloses the use of PEG to form granules suitable for the preparation of tablets. Rieglman et al. (U.S. Pat. No. 4,151,273) discloses a method of enhancing systemic absorption of poorly soluble drugs by forming a glossy solid matrix of the carrier (PEG) and the drug. A solution of the drug and the carrier is formed at an elevated temperature, with or without a solvent, and chilled rapidly to form a solid mass which can be ground to a powder.
Leeson (U.S. Pat. No. 3,862,311) discloses increased absorption of drugs when they are combined with carrier (PEG) and surfactant. See Col. 2, lines 3-9 and Col. 2, lines 48-58 for discussion of carriers used and of drug-surfactant-carrier ratios, respectively. Halpern et al. (U.S. Pat. No. 2,698,822) disclose PEG used to increase systemic absorption of insoluble drugs. Lowry et al. (U.S. Pat. No. 3,308,217) disclose a dry granulation method of preparing a mix for producing tablets using PEG (See Col. 4, lines 36-44), which employs a heating step. Chapura (U.S. Pat. No. 3,932,613) claims a PEG suppository.